14-22519994-C-G

Variant names:

• chr14-22519994-C-G
• rs1483979
• ENST00000390513.1:c.24C>G

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The ENST00000390513.1(TRAJ24):​c.24C>G​(p.Phe8Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.822 in 760,414 control chromosomes in the GnomAD database, including 259,710 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.85 (55548 hom., cov: 27)
  • Exomes 𝑓: 0.81 (204162 hom.)
• Consequence: TRAJ24 ENST00000390513.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.04
• Publications: 12 publications found

Genes affected

TRAJ24 (HGNC:12053): (T cell receptor alpha joining 24) T cell receptors recognize foreign antigens which have been processed as small peptides and bound to major histocompatibility complex (MHC) molecules at the surface of antigen presenting cells (APC). Each T cell receptor is a dimer consisting of one alpha and one beta chain or one delta and one gamma chain. In a single cell, the T cell receptor loci are rearranged and expressed in the order delta, gamma, beta, and alpha. If both delta and gamma rearrangements produce functional chains, the cell expresses delta and gamma. If not, the cell proceeds to rearrange the beta and alpha loci. This region represents the germline organization of the T cell receptor alpha and delta loci. Both the alpha and delta loci include V (variable), J (joining), and C (constant) segments and the delta locus also includes diversity (D) segments. The delta locus is situated within the alpha locus, between the alpha V and J segments. During T cell development, the delta chain is synthesized by a recombination event at the DNA level joining a D segment with a J segment; a V segment is then joined to the D-J gene. The alpha chain is synthesized by recombination joining a single V segment with a J segment. For both chains, the C segment is later joined by splicing at the RNA level. Recombination of many different V segments with several J segments provides a wide range of antigen recognition. Additional diversity is attained by junctional diversity, resulting from the random additional of nucleotides by terminal deoxynucleotidyltransferase. Five variable segments can be used in either alpha or delta chains and are described by TRAV/DV symbols. Several V and J segments of the alpha locus are known to be incapable of encoding a protein and are considered pseudogenes. [provided by RefSeq, Aug 2016]

TRA (HGNC:12027):

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.44).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.926 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRAJ24	unassigned_transcript_2283	c.24C>G	p.Phe8Leu	missense_variant	Exon 1 of 1
TRA		n.22519994C>G		intragenic_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRAJ24	ENST00000390513.1	c.24C>G	p.Phe8Leu	missense_variant	Exon 1 of 1	6		ENSP00000452134.1

Frequencies

GnomAD3 genomes AF: 0.851 AC: 129023 AN: 151670 Hom.: 55482 Cov.: 27

Gnomad AFR AF: 0.934

Gnomad AMI AF: 0.964

Gnomad AMR AF: 0.814

Gnomad ASJ AF: 0.849

Gnomad EAS AF: 0.471

Gnomad SAS AF: 0.782

Gnomad FIN AF: 0.781

Gnomad MID AF: 0.820

Gnomad NFE AF: 0.851

Gnomad OTH AF: 0.862

GnomAD4 exome AF: 0.814 AC: 495601 AN: 608626 Hom.: 204162 Cov.: 0 AF XY: 0.814 AC XY: 270710 AN XY: 332446

African (AFR) AF: 0.932 AC: 16370 AN: 17570

American (AMR) AF: 0.774 AC: 33268 AN: 42992

Ashkenazi Jewish (ASJ) AF: 0.850 AC: 17761 AN: 20886

East Asian (EAS) AF: 0.517 AC: 18434 AN: 35670

South Asian (SAS) AF: 0.787 AC: 53783 AN: 68382

European-Finnish (FIN) AF: 0.802 AC: 30973 AN: 38600

Middle Eastern (MID) AF: 0.817 AC: 3314 AN: 4054

European-Non Finnish (NFE) AF: 0.847 AC: 294590 AN: 347702

Other (OTH) AF: 0.827 AC: 27108 AN: 32770

GnomAD4 genome AF: 0.851 AC: 129150 AN: 151788 Hom.: 55548 Cov.: 27 AF XY: 0.843 AC XY: 62516 AN XY: 74164

African (AFR) AF: 0.934 AC: 38654 AN: 41382

American (AMR) AF: 0.814 AC: 12423 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.849 AC: 2943 AN: 3466

East Asian (EAS) AF: 0.471 AC: 2413 AN: 5122

South Asian (SAS) AF: 0.782 AC: 3751 AN: 4796

European-Finnish (FIN) AF: 0.781 AC: 8227 AN: 10534

Middle Eastern (MID) AF: 0.823 AC: 242 AN: 294

European-Non Finnish (NFE) AF: 0.851 AC: 57793 AN: 67916

Other (OTH) AF: 0.864 AC: 1827 AN: 2114

Alfa AF: 0.832 Hom.: 5723

Bravo AF: 0.855

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.44
CADD	Benign	15
PhyloP100		1.0

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1483979; hg19: chr14-22988972;